A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies

Registration Number
NCT06634589
Lead Sponsor
BeiGene
Brief Summary

The purpose of this study is to measure the safety, preliminary antitumor activity, pharmacokinetics, and pharmacodynamics with BGB-16673 in combination with other agents in participants with relapsed or refractory (R/R) B-cell malignancies. This study is structured as a master protocol with separate substudies. This study will initially include two substudi...

Detailed Description

This new study will check how safe and helpful a potential anticancer drug called BGB-16673 is in participants with R/R B-cell malignancies when it is given in combination with other medicines - sonrotoclax in substudy 1, and with zanubrutinib in substudy 2.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
170
Inclusion Criteria
  • Must sign the informed consent form (ICF) and be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the ICF

  • Confirmed diagnosis of a R/R B-cell malignancy

  • Protocol-defined measurable disease

  • Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2

  • Adequate organ function

  • Female participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for 30 days after the last dose of BGB-16673 or zanubrutinib, or 90 days after the last dose of sonrotoclax. A negative urine or serum pregnancy test result must be provided 10-14 days before the first dose of study treatment

  • Nonsterile male participants must be willing to use a highly effective method of birth control and refrain from sperm donation for the duration of the study and for 30 days after the last dose of BGB-16673 or zanubrutinib, or 90 days after the last dose of sonrotoclax

  • Substudy 2 Inclusion Criteria:

    • Bruton tyrosine kinase (BTK) inhibitor-naive, or
    • Previously received treatment with a covalent BTK inhibitor and discontinued for reasons other than clinical progression

Key

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Exclusion Criteria
  • Treatment-naive B-cell malignancies

  • Unable to comply with the requirements of the protocol

  • Active leptomeningeal disease or uncontrolled, untreated brain metastasis

  • Any malignancy ≤ 2 years before first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively

  • Autologous stem cell transplant ≤ 3 months prior to screening or chimeric antigen T-cell therapy ≤ 3 months prior to screening

  • Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent

  • Participants who have a history of severe allergic reactions or hypersensitivity to the active ingredient and excipients of BGB-16673, sonrotoclax, or zanubrutinib

  • Substudy 1 Exclusion Criterion:

    • Prior treatment with a B-cell lymphoma-2 (Bcl-2) inhibitor
  • Substudy 2 Exclusion Criterion:

    • Participants who discontinued prior zanubrutinib treatment due to intolerance

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Substudy 1 Part 1b: Safety ExpansionBGB-16673Cohorts of select dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell histologies.
Substudy 1 Part 1b: Safety ExpansionsonrotoclaxCohorts of select dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell histologies.
Substudy 2 Part 1a: Dose EscalationBGB-16673Sequential cohorts of increasing dose level combinations of BGB-16673 and zanubrutinib will be evaluated.
Substudy 2 Part 1a: Dose EscalationZanubrutinibSequential cohorts of increasing dose level combinations of BGB-16673 and zanubrutinib will be evaluated.
Substudy 2 Part 1b: Safety ExpansionBGB-16673Cohorts of select dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell histologies.
Substudy 1 Part 1a: Dose EscalationBGB-16673Sequential cohorts of increasing dose level combinations of BGB-16673 and sonrotoclax will be evaluated.
Substudy 1 Part 1a: Dose EscalationsonrotoclaxSequential cohorts of increasing dose level combinations of BGB-16673 and sonrotoclax will be evaluated.
Substudy 2 Part 1b: Safety ExpansionZanubrutinibCohorts of select dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell histologies.
Primary Outcome Measures
NameTimeMethod
Substudy 1 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse eventsFrom the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Substudy 1 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse eventsFrom the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Substudy 2 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse eventsFrom the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Substudy 2 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse eventsFrom the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Secondary Outcome Measures
NameTimeMethod
Substudy 1 Part 1a and 1b: Overall Response Rate (ORR) for BGB-16673 and sonrotoclaxUp to approximately 3 years

ORR is defined as the percentage of participants with complete response (CR) or partial response (PR)

Substudy 1 Part 1a and 1b: Duration of Response (DOR) for BGB-16673 and sonrotoclaxUp to approximately 3 years

DOR is defined as the time from the first objective response to disease progression documented after treatment initiation or death, whichever occurs first.

Substudy 1 Part 1a and 1b: Time to Response (TTR) for BGB-16673 and sonrotoclaxUp to approximately 3 years

TTR is defined as the time from treatment initiation to first response

Substudy 1 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and sonrotoclaxFrom Week 1 to Week 17
Substudy 1 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and sonrotoclaxFrom Week 1 to Week 17
Substudy 1 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and sonrotoclaxFrom Week 1 to Week 17
Substudy 1 Part 1a: Terminal half-life (t1/2) of BGB-16673 and sonrotoclaxFrom Week 1 to Week 17
Substudy 1 Part 1a: Trough concentration (Ctrough) of BGB-16673 and sonrotoclaxFrom Week 1 to Week 17
Substudy 1 Part 1b: Number of patients with complete response or complete response with incomplete count recovery (CR/CRi) who achieve undetectable minimal residual disease (uMRD)Up to approximately 3 years
Substudy 2 Part 1a and 1b: ORR for BGB-16673 and zanubrutinibUp to approximately 3 years

ORR is defined as the percentage of participants with complete response (CR) or partial response (PR)

Substudy 2 Part 1a and 1b: DOR for BGB-16673 and zanubrutinibUp to approximately 3 years

DOR is defined as the time from the first objective response to disease progression documented after treatment initiation or death, whichever occurs first.

Substudy 2 Part 1a and 1b: TTR for BGB-16673 and zanubrutinibUp to approximately 3 years

TTR is defined as the time from treatment initiation to the first response.

Substudy 2 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and zanubrutinibFrom Week 1 to Week 17
Substudy 2 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and zanubrutinibFrom Week 1 to Week 17
Substudy 2 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and zanubrutinibFrom Week 1 to Week 17
Substudy 2 Part 1a: Terminal half-life (t1/2) of BGB-16673 and zanubrutinibFrom Week 1 to Week 17
Substudy 2 Part 1a: Trough concentration (Ctrough) of BGB-16673 and zanubrutinibFrom Week 1 to Week 17

Trial Locations

Locations (43)

Mayo Clinic Jacksonville

🇺🇸

Jacksonville, Florida, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

University of Michigan Health System

🇺🇸

Ann Arbor, Michigan, United States

Mayo Clinic Rochester

🇺🇸

Rochester, Minnesota, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Summit Medical Group

🇺🇸

Florham Park, New Jersey, United States

Weill Cornell Medical College Newyork Presbyterian Hospital

🇺🇸

New York, New York, United States

Icahn School of Medicine At Mount Sinai

🇺🇸

New York, New York, United States

Memorial Sloan Kettering Cancer Center Mskcc

🇺🇸

New York, New York, United States

University of Rochester

🇺🇸

Rochester, New York, United States

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

The University of Texas Md Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Huntsman Cancer Institute

🇺🇸

Salt Lake City, Utah, United States

University of Wisconsin

🇺🇸

Madison, Wisconsin, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

St George Hospital

🇦🇺

Kogarah, New South Wales, Australia

Mater Cancer Care Centre

🇦🇺

South Brisbane, Queensland, Australia

Monash Health

🇦🇺

Clayton, Victoria, Australia

Peter Maccallum Cancer Centre

🇦🇺

Melbourne, Victoria, Australia

The Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

Linear Clinical Research

🇦🇺

Nedlands, Western Australia, Australia

Fujian Medical University Union Hospital

🇨🇳

Fuzhou, Fujian, China

Sun Yat Sen University Cancer Center

🇨🇳

Guangzhou, Guangdong, China

The First Affiliated Hospital of Soochow University

🇨🇳

Suzhou, Jiangsu, China

The First Affiliated Hospital, Zhejiang University School of Medicinechengzhan

🇨🇳

Hangzhou, Zhejiang, China

The First Affiliated Hospital of Wenzhou Medical University

🇨🇳

Wenzhou, Zhejiang, China

Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden

🇩🇪

Dresden, Germany

Universitatsklinikum Jena Klinik Fur Innere Medizin Ii

🇩🇪

Jena, Germany

Universitatsklinikum Schleswig Holstein, Campus Kiel

🇩🇪

Kiel, Germany

Medizinische Universitaetsklinik

🇩🇪

Tuebingen, Germany

Universitaetsklinikum Ulm, Innere Medizin Iii

🇩🇪

Ulm, Germany

Azienda Ospedaliera Universitaria Policlinico Santorsola Malpighi

🇮🇹

Bologna, Italy

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

🇮🇹

Milano, Italy

Istituto Nazionale Tumori Fondazione G Pascale

🇮🇹

Napoli, Italy

Istituto Clinico Humanitas

🇮🇹

Rozzano, Italy

Centro Ricerche Cliniche Di Verona

🇮🇹

Verona, Italy

Auckland City Hospital

🇳🇿

Auckland, New Zealand

North Shore Hospital

🇳🇿

Takapuna, New Zealand

Uniwersyteckie Centrum Kliniczne

🇵🇱

Gdansk, Poland

Samodzielny Publiczny Szpital Kliniczny Nr W Lublinie

🇵🇱

Lublin, Poland

Szpital Kliniczny Mswia Z Warmisko Mazurskim Centrum Onkologii

🇵🇱

Olsztyn, Poland

Szpital Wojewodzki W Opolu Sp Z Oo Oddzia Hematologii I Onkologii Hematologicznej

🇵🇱

Opole, Poland

Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Hematology Unit

🇵🇱

Warsaw, Poland

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